ACSF3: Acyl-CoA Synthetase Family Member 3
Mitochondrial malonyl-CoA synthetase involved in fatty acid metabolism and associated with combined malonic and methylmalonic aciduria (CMAMMA)
Gene Information Card
| Symbol | ACSF3 |
|---|---|
| Full Name | Acyl-CoA Synthetase Family Member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q24.3 |
| NCBI Gene ID | 197322 ncbi.nlm.nih.gov/gene/197322 |
| Ensembl ID | ENSG00000176715 |
| UniProt ID | Q4G176 |
| OMIM ID | 614245 |
| HGNC ID | 26696 |
| Aliases | MGC2650, FLJ22662, malonyl-CoA synthetase |
Description
ACSF3 encodes a mitochondrial acyl-CoA synthetase that catalyzes the conversion of malonate to malonyl-CoA, a key step in mitochondrial fatty acid synthesis. Mutations in this gene cause combined malonic and methylmalonic aciduria (CMAMMA), an autosomal recessive disorder characterized by elevated malonic and methylmalonic acid levels. The enzyme is distinct from cytosolic malonyl-CoA synthetase and plays a critical role in mitochondrial metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Combined malonic and methylmalonic aciduria (CMAMMA) | Loss-of-function mutations in ACSF3 impair malonyl-CoA synthesis, leading to accumulation of malonic and methylmalonic acid in urine and plasma. | ClinVar, OMIM #614265 |
| Malonic aciduria | Deficient ACSF3 activity disrupts mitochondrial fatty acid synthesis, causing malonic acid accumulation. | OMIM #614245 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Kidney | 9.8 | Medium |
| Heart | 7.5 | Low |
| Brain | 6.2 | Low |
| Skeletal Muscle | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.2 | Hepatocellular carcinoma cell line |
| HEK293 | 11.5 | Embryonic kidney cells |
| K562 | 8.9 | Chronic myelogenous leukemia cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1672C>T (p.Arg558*) | Nonsense | Rare | Loss of function; associated with CMAMMA |
| c.1031A>G (p.Tyr344Cys) | Missense | Rare | Likely pathogenic; reduced enzyme activity |
| c.1990C>T (p.Arg664Trp) | Missense | Rare | Uncertain significance; reported in CMAMMA patients |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg558*) reduce or abolish malonyl-CoA synthetase activity, leading to CMAMMA.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003987 - malonyl-CoA synthetase activity | • GO:0005739 - mitochondrion |
| • GO:0006633 - fatty acid biosynthetic process | • GO:0016874 - ligase activity |
| • GO:0005524 - ATP binding |
Pathways
• Mitochondrial fatty acid synthesis (malonyl-CoA pathway)
• Metabolism of malonate and methylmalonate
Protein Summary
ACSF3 is a 576-amino acid mitochondrial protein that functions as a malonyl-CoA synthetase, converting malonate to malonyl-CoA using ATP. It is essential for mitochondrial fatty acid synthesis and is distinct from the cytosolic enzyme. Defects in this protein cause combined malonic and methylmalonic aciduria (CMAMMA), a rare metabolic disorder.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACSF3 Knockout HEK293 Cell Line | EDJ-KQ12263 | Human | 197322 | Details Get a Quote |
| ACSF3 Knockout A-549 Cell Line | EDJ-KQ41060 | Human | 197322 | Details Get a Quote |
| ACSF3 Knockout HCT 116 Cell Line | EDJ-KQ41061 | Human | 197322 | Details Get a Quote |
| ACSF3 Knockout HeLa Cell Line | EDJ-KQ39821 | Human | 197322 | Details Get a Quote |
| ACSF3 Knockout AGS Cell Line | EDJ-KZ524 | Human | 197322 | Details Get a Quote |
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